Optimization of compound K extraction using natural deep eutectic solvents and evaluation of mitochondrial protective activity
- 1Invivotec Co., Ltd., Seongnam, 13449, Republic of Korea.
- 2Department of Convergent Biotechnology and Advanced Materials Science, Graduate School of Biotechnology, Kyung Hee University, Global Campus, Yongin, Gyeonggi-do, 17104, Republic of Korea.
Abstract
Background: Compound K (CK), a deglycosylated ginsenoside metabolite, exhibits high bioavailability and diverse pharmacological activities but has limited solubility in conventional solvents. Natural Deep Eutectic Solvents (NADES) composed of Generally Recognized as Safe (GRAS) compounds provide an eco-friendly alternative for efficient CK extraction. Methods: A full factorial design was applied to optimize CK dissolution. Three variables—hydrogen bond donor (HBD; glycerol, 1,3-propanediol, butylene glycol), solvent ratio (betaine: HBD = 1:1 or 1:2), and water content (0–20%)—were evaluated. CK concentration was quantified by HPLC, and the optimized NADES was validated through triplicate experiments. Mitochondrial membrane potential (Δψm) was assessed in zebrafish embryos using JC-1 fluorescence to compare the bioactivity of CK extracts obtained with NADES, 50% ethanol, and water. Results: Water content significantly affected CK extraction ( p < 0.05). The optimized NADES (betaine:1,3-propanediol = 1:2, 20% water) yielded 339.5 μg/mL CK at 3 mg/mL loading concentration. Confirmation experiments showed excellent reproducibility (339.2 ± 0.9 μg/mL). Comparative validation demonstrated that NADES achieved 1.30–1.40-fold higher extraction efficiency than water and 1.09–1.27-fold higher than 50% ethanol across all tested concentrations (3, 5, and 10 mg/mL). CK-NADES extracts exhibited superior mitochondrial protection (EC 50 = 1.10 μg/mL) compared with 50% ethanol (EC 50 not reached) and water (not detectable). Conclusion: Betaine–1,3-propanediol NADES significantly enhanced CK extraction efficiency and mitochondrial protective activity. This study establishes NADES as a sustainable and effective green-chemistry platform for developing CK-enriched cosmeceutical and functional food formulations.
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BibTeX
@article{nam2026optimization,
title = {{Optimization of compound K extraction using natural deep eutectic solvents and evaluation of mitochondrial protective activity}},
author = {Youn Hee Nam and Gyeong Jin Seo and Ji Young Kang and Nevedita Murughanantham and Na Woo Kim and Sung Woo Shin and Min Ji Park and Subha Pandian and Soo Mi Ahn and Bin Na Hong and Tong Ho Kang},
journal = {Journal of Ginseng Research},
year = {2026},
month = aug,
doi = {10.1016/j.jgr.2026.101147},
url = {https://doi.org/10.1016/j.jgr.2026.101147},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Optimization of compound K extraction using natural deep eutectic solvents and evaluation of mitochondrial protective activity
AU - Youn Hee Nam
AU - Gyeong Jin Seo
AU - Ji Young Kang
AU - Nevedita Murughanantham
AU - Na Woo Kim
AU - Sung Woo Shin
AU - Min Ji Park
AU - Subha Pandian
AU - Soo Mi Ahn
AU - Bin Na Hong
AU - Tong Ho Kang
PY - 2026
DA - 2026/08/21
JO - Journal of Ginseng Research
DO - 10.1016/j.jgr.2026.101147
UR - https://doi.org/10.1016/j.jgr.2026.101147
AB - Background: Compound K (CK), a deglycosylated ginsenoside metabolite, exhibits high bioavailability and diverse pharmacological activities but has limited solubility in conventional solvents. Natural Deep Eutectic Solvents (NADES) composed of Generally Recognized as Safe (GRAS) compounds provide an eco-friendly alternative for efficient CK extraction. Methods: A full factorial design was applied to optimize CK dissolution. Three variables—hydrogen bond donor (HBD; glycerol, 1,3-propanediol, butylene glycol), solvent ratio (betaine: HBD = 1:1 or 1:2), and water content (0–20%)—were evaluated. CK concentration was quantified by HPLC, and the optimized NADES was validated through triplicate experiments. Mitochondrial membrane potential (Δψm) was assessed in zebrafish embryos using JC-1 fluorescence to compare the bioactivity of CK extracts obtained with NADES, 50% ethanol, and water. Results: Water content significantly affected CK extraction ( p < 0.05). The optimized NADES (betaine:1,3-propanediol = 1:2, 20% water) yielded 339.5 μg/mL CK at 3 mg/mL loading concentration. Confirmation experiments showed excellent reproducibility (339.2 ± 0.9 μg/mL). Comparative validation demonstrated that NADES achieved 1.30–1.40-fold higher extraction efficiency than water and 1.09–1.27-fold higher than 50% ethanol across all tested concentrations (3, 5, and 10 mg/mL). CK-NADES extracts exhibited superior mitochondrial protection (EC 50 = 1.10 μg/mL) compared with 50% ethanol (EC 50 not reached) and water (not detectable). Conclusion: Betaine–1,3-propanediol NADES significantly enhanced CK extraction efficiency and mitochondrial protective activity. This study establishes NADES as a sustainable and effective green-chemistry platform for developing CK-enriched cosmeceutical and functional food formulations.
SN - 1226-8453
SN - 2093-4947
ER -